1. Field of Invention
This invention is related to mass spectrometry of biological samples. More specifically, this invention is related to the use of ambient pressure matrix-assisted laser desorption/ionization technique in mass spectrometry imaging applications.
2. Discussion of the Background
Ambient pressure (AP—also sometimes referred to as atmospheric pressure) matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is a standard technique for producing ions from labile molecules, especially biological molecules [see Laiko et al., U.S. Pat. No. 5,965,884; and Bai et al., U.S. Pat. No. 6,849,847, the entire contents of which are incorporated herein by reference]. It is widely used in MS imaging (MSI) applications used for studying spatial distribution of biomolecules in special samples—biological tissues. Typically, the definition of the ambient pressure range includes the pressure from 0.1 Torr to 2,000 Torr.
AP ion sources can utilize different ionization techniques, which in addition to AP-MALDI also include electrospray ionization (ESI), AP chemical ionization (APCI), direct analysis in real time (DART), AP photoionization (APPI), desorption ESI (DESI), secondary ESI (s-ESI) etc. Small molecules can be ionized without a matrix (so-called direct laser ionization or DLI) and also using nanostructure-assisted laser desorption/ionization (NALDI), surface-enhanced laser/desorption ionization (SELDI), or desorption/ionization on silicon (DIOS) techniques. The AP ion sources have been used with mass spectrometers having atmospheric pressure interfaces (API) for the introduction of ions generated at ambient pressure conditions into the vacuum of mass spectrometers. The interchangeability of AP sources (meaning that different AP sources can be attached to the same MS typically within few minutes) and the wealth of ionization techniques available at AP conditions make mass spectrometers with API attractive and widely popular. AP ion sources are also used in ion mobility spectrometry (IMS) separating ions based on different gas phase mobility of ions while the ions are drifting in electric fields.
The requirement of interchangeability in conventional AP-MALDI design usually required an optical fiber for connecting a laser to an AP-MALDI ionization chamber. The laser spot size on the sample in such an AP-MALDI design is usually determined by the diameter of the optical fiber used (typically in the 100-500 μm range).
The subject matters of the patents, patent applications, and articles described herein are all incorporated by reference in their entirety herein.